Disorder Category

Screening

Finding

Tested By

Overview

Deficiency of phenylalanine hydroxylase (PAH), the enzyme responsible for converting phenylalanine to tyrosine, results in
accumulation of phenylalanine (Phe) with toxic effects on brain development.

Prevalence

The incidence of PKU in the U.S. is approximately 1:23,000 births, although in the African-American population, incidence
is about 1:50,000. [Therrell: 2014]

Inheritance

Autosomal recessive

Maternal & Family History

Benign forms of PKU can present with minimal elevations of phenylalanine levels (maximal plasma phenylalanine <360 micromolar),
cause no symptoms, and require no therapy. Mild forms of phenylketonuria can present with slightly increased phenylalanine
levels (maximal plasma phenylalanine 360-1000 micromolar), are usually easy to control with diet, and respond to therapy with
sapropterin. Yet, children born to women with PKU are at risk for "maternal PKU" because high levels of phenylalanine are
teratogenic.

Elevated phenylalanine levels can be caused by defects in the synthesis or recycling of tetrahydrobiopterin, an essential
co-factor of phenylalanine hydroxylase. Since tetrahydrobiopterin is also a cofactor of other enzymes involved in neurotransmitter
synthesis, at-risk patients need to be identified as soon as possible to start appropriate therapy.

Prenatal Testing

DNA testing by amniocentesis or CVS

Clinical Characteristics

With treatment by early introduction and maintenance of special diet, normal IQ and development can be expected. Without treatment, patients with classic PKU have no symptoms at birth, but usually develop them by 6 months of age.

Initial symptoms may include:

A musty or "mousy" odor of the body and urine

Developmental delays in sitting, crawling, and standing

Microcephaly

If patients remain untreated they may develop:

Decreased skin and hair pigmentation (due to lack of tyrosine)

Eczema

Seizures

Profound mental retardation

A diet low in protein and phenylalanine needs to be continued for life. [Camp: 2014] The diet needs to be supplemented with tyrosine, which becomes an essential amino acid in this condition. With relaxation
of diet, patients have increased deficits in executive function, attention deficit disorder and problems in school. Some patients
respond to therapy with tetrahydrobiopterin, the cofactor of phenylalanine hydroxylase that stimulates residual enzyme activity
in responsive mutant enzymes.

Genetics in Primary Care Institute (AAP)The goal of this site is to increase collaboration in the care of children with known or suspected genetic disorders. Includes
health supervision guidelines and other useful resources; a collaboration among the Health Resources & Services Administration,
the Maternal and Child Health Bureau, and the American Academy of Pediatrics.

For Parents and Patients

Support

General

PKU Information - Information for Parents (STAR-G)A fact sheet, written by a genetic counselor and reviewed by metabolic and genetic specialists, for families who have received
an initial diagnosis of a newborn disorder; Screening, Technology and Research in Genetics.

PKU (Genetics Home Reference)Excellent, detailed review of condition for patients and families; sponsored by the U.S. National Library of Medicine.

National Urea Cycle Disorders FoundationThis non-profit organization provides support services and information for families; medical lectures on urea cycle disorders;
nutrition and medication resources; and information about events and conferences.